Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: reduction of Wnt-associated proteins and reduced translocation of galectin-3-mediated β-catenin to the nucleus.
Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: reduction of Wnt-associated proteins and reduced translocation of galectin-3-mediated β-catenin to the nucleus.
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DOI：
10.1002/jcb.23326
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发表时间：
2012-01
影响因子：
4
通讯作者：
Patmasiriwat, Pimpicha
中科院分区：
文献类型：
--
作者：
Dakeng, Sumana;Duangmano, Suwit;Jiratchariyakul, Weena;U-Pratya, Yaowalak;Boegler, Oliver;Patmasiriwat, Pimpicha
葫芦素是在葫芦科植物中发现的四环三萜。葫芦素已被证明具有抗癌和抗炎活性。研究了从泰国药用植物trichosans cucumerina Linn中提取的葫芦素B的抗癌活性。采用MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑）测定法测定细胞活力。结果表明，黄瓜T. cucumerina Linn.中含有葫芦素B。对乳腺癌细胞株SKBR-3和MCF-7具有细胞毒作用，IC50分别为4.60和88.75 μg/ml。生长抑制归因于G2/M期阻滞和细胞凋亡。Cyclin D1、c-Myc和β-catenin表达水平降低。Western blot分析显示，PARP裂解增加，wnt相关信号分子β-catenin、半乳糖凝集素-3、cyclin D1和c-Myc减少，磷酸化GSK-3β水平发生相应变化。葫芦素B抑制β-catenin和半乳糖凝集素-3向细胞核的易位。细胞蛋白分离证实了细胞核中β-连环蛋白和半乳糖凝集素-3的缺失。t细胞因子(TCF)/淋巴细胞增强因子（LEF）依赖的转录活性在葫芦素B处理的细胞中被破坏。用葫芦素B化合物处理细胞24小时后，荧光素酶的相对活性降低。我们的数据表明葫芦素B可能通过阻断Wnt信号通路部分诱导细胞凋亡并发挥生长抑制作用。
The cucurbitacins are tetracyclic triterpenes found in plants of the family Cucurbitaceae. Cucurbitacins have been shown to have anticancer and anti-inflamatory activities. We investigated the anticancer activity of cucurbitacin B extracted from Thai medicinal plant Trichosanthes cucumerina Linn. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results indicated that cucurbitacin B from T. cucumerina Linn. has a cytotoxic effect on breast cancer cell lines SKBR-3 and MCF-7 with an IC50 of 4.60 and 88.75 μg/ml, respectively. Growth inhibition was attributed to G2/M phase arrest and apoptosis. Cyclin D1, c-Myc and β-catenin expression levels were reduced. Western blot analysis showed increased PARP cleavage and decreased Wnt-associated signaling molecules β-catenin, galectin-3, cyclin D1 and c-Myc, and corresponding changes in phosphorylated GSK-3β levels. Cucurbitacin B treatment inhibited translocation to the nucleus of β-catenin and galectin-3. The depletion of β-catenin and galectin-3 in the nucleus was confirmed by cellular protein fractionation. T-cell factor (TCF)/lymphoid enhancer factor (LEF)-dependent transcriptional activity was disrupted in cucurbitacin B treated cells as tested by a TCF reporter assay. The relative luciferase activity was reduced when we treated cells with cucurbitacin B compound for 24 hours. Our data suggest that cucurbitacin B may in part induce apoptosis and exert growth inhibitory effect via interruption the Wnt signaling.
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DOI：
10.1023/b:jomg.0000037157.94207.33
发表时间：
2004-04-01
影响因子：
2.5
作者：
Brennan, KR;Brown, AMC
通讯作者：
Brown, AMC
影响因子：
9.7
作者：
Chan, Kin Tak;Li, Kwan;Xie, Wei Dong
通讯作者：
Xie, Wei Dong
影响因子：
9.7
作者：
Jayaprakasam, B;Seeram, NP;Nair, MG
通讯作者：
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影响因子：
4.8
作者：
Ling, X;Bernacki, RJ;Li, FZ
通讯作者：
Li, FZ
影响因子：
7.4
作者：
Brown, A M
通讯作者：
Brown, A M